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Updated: Jul 5, 2025

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
USP5 facilitates bladder cancer progression by stabilizing the c-Jun protein
Hui-Hui Zhang1, An-Qi Zhang1, Peng Peng1
1Department of Laboratory Medicine, Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Hunan Normal University School of Medicine, 371 Tongzipo Road, Yuelu District, Changsha, Hunan, China.
High USP5 expression promotes bladder cancer by stabilizing c-Jun. Inhibiting USP5 could be a new therapeutic strategy for bladder cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Bladder cancer is a significant global health concern with increasing mortality rates.
- The molecular underpinnings of bladder cancer require further investigation.
- Deubiquitinating enzymes (DUBs), particularly USP5, are implicated in various cancers, but their role in bladder cancer is underexplored.
Purpose of the Study:
- To investigate the role and mechanism of USP5 in bladder cancer progression.
- To determine if USP5 is a potential therapeutic target for bladder cancer.
Main Methods:
- USP5 expression analysis using GEPIA.
- Creation of USP5-knockout and USP5-overexpressing bladder cancer cell lines.
- In vitro assays (CCK8, colony formation, transwell, scratch) and in vivo xenograft models to assess cellular behavior.
- RNA sequencing, dual-luciferase reporter assays, co-immunoprecipitation, immunofluorescence, and cycloheximide chase assays to elucidate molecular mechanisms.
Main Results:
- USP5 expression is elevated in bladder cancer patients.
- USP5 depletion significantly impedes bladder cancer cell proliferation, viability, and migration in vitro and in vivo.
- USP5 activates JNK signaling by interacting with and stabilizing c-Jun through inhibition of its ubiquitination.
Conclusions:
- Elevated USP5 expression drives bladder cancer progression by stabilizing c-Jun.
- USP5 represents a promising therapeutic target for bladder cancer treatment.
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